Many therapeutic polypeptides are formulated in aqueous solution because they are most active in this form. However, most polypeptides are not particularly stable in aqueous solution, such that the formulations often have a short half-life and require refrigeration. Although aqueous solutions of polypeptides can be dried by freeze-drying, spray-drying or other methods, such dried formulations may also be unstable and have reduced activity relative to an aqueous solution of the polypeptide. Typical break-down mechanisms that occur both in aqueous solution and in dried formulations include aggregation and oxidative or hydrolytic degradation. Thus, the majority of therapeutic polypeptides, whether in aqueous solution or dried, are stored under refrigerated conditions due to their limited stability.
Linaclotide is a peptide having the amino acid sequence Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: 1) that activates the guanylate cyclase-C (GC-C) receptor. Linaclotide, which may be administered orally, is useful for the treatment of gastrointestinal disorders and conditions, including irritable bowel syndrome (IBS) and chronic constipation (CC). Formulations comprising linaclotide have needed to be refrigerated in order to avoid degradation over time. However, refrigeration is inconvenient both for commercial distribution of the drug and for storage by patients. Thus, there is a need to have a solid linaclotide formulation that is stable at room temperature for at least 12 months.